Area of interest

My laboratory combines molecular, cellular, in vivo and translational approaches to define mechanisms by which growth factors and cytokines impact on gastrointestinal growth disease and obesity.

The normal intestine constantly renews its epithelial lining by high rates of cell proliferation and co-ordinated patterns of cell differentiation and apoptosis. Abnormalities in intestinal growth occur in colon cancer, ulcerative colitis, Crohn's disease and in patients receiving chemo- or radiation therapy for cancer. We use model intestinal cell lines, mutant mice engineered to overexpress or underexpress growth factors or signaling molecules which mediate or terminate growth factor action, and models with reporter genes knocked into stem cell loci. We test these mutants in experimental models of cancer, inflammatory bowel disease and radiation therapy. We are attempting to define: a) which intracellular signaling pathways and genes mediate growth factor action on intestine in normal and disease states, b) how growth factors interact with cytokines derived from immune cells to promote normal or aberrant tissue healing after damage or inflammation, c) the role of stem cells in intestinal responses to growth factors and disease, and d) how aberrant responses lead to early stage cancer. Our laboratory has recently demonstrated that suppressors of cytokine signaling (SOCs) have tumor suppressor roles in the intestine and control aberrant healing (to limit formation of internal scars). In addition to basic approaches in animal models, a theme of the lab is to "translate" our studies to human samples. We therefore perform epidemiological analyses to ensure clinical relevance of our basic science findings. A new line of research stems from interactions with faculty in interdisciplinary obesity predoctoral and postdoctoral training grants. In this research, we are investigating the role of diet and bacteria interactions in obesity and intestinal inflammation.